GENOMICS AND GENE TARGETING CORE: Director - K. Kaestner Diabetes mellitus is a highly significant health problem, affecting approximately 18 million people in the United States alone. Our understanding of the pathogenesis of diabetes has benefited immensely from the molecular genetic analysis of the disease both in human and in rodent models. Advances in microarray technology have enabled investigators in the fields of diabetes and endocrinology to simultaneously analyze the expression levels of thousands of genes, the only limitation being the high cost of the commercial microarrays. During the past grant cycle we have established a well-utilized Core to serve the DERC's functional genomics needs. We now propose to expand the scope of the Core to also include gene targeting in mouse embryonic stem cells, as this would aid the research efforts of multiple DERC members. To reflect this change in mission, the Core has been renamed "Genomics and Gene Targeting" Core. The Core will offer the following services: a) provide both 70mer oligo and cDNA microarrays for gene expression analysis using mouse and human samples b) hybridization of both Affymetrix, oligo, cDNA and promoter arrays c) develop, hybridize and analyze promoter/enhancer arrays for global location analysis of transcription factor occupancy d) analysis of microarray data and training of Center investigators in expression profiling and location analysis e) design and construction of gene targeting vectors and f) culture, electroporation and selection of mouse embryonic stems cells for the introduction of targeted mutations. The Core will interact closely with the other DERC cores, in particular the Mouse Phenotyping, Physiology and Metabolism Core (Rex Ahima) and the Transgenic and Chimeric Mouse Core (Nancy Cooke). Correlation of the phenotypic analysis performed on genetically altered or metabolically challenged mice with their expression profile will greatly enhance the power of each individual analysis.